Polynucleotides typified by polyinosinic—polycytidylic acid, i.e., poly(I)-poly(C), are well-known compounds in the art, and the potentiality as a medicine for treating hepatitis or cancer have been investigated in view of their interferon inducing action, immune activating action, and the like.
The pharmacological action of these polynucleotides has high correlation with the chain length, and longer the chain length, stronger the interferon inducing action and the like. On the other hang, longer the chain length, stronger the toxicity manifested.
Recently, there has been an approach for reducing toxicity with maintaining useful pharmacological action of a polynucleotide, by a method wherein a synthetic polynucleotide having a relatively shorter chain prepared by the hydrolysis of a polynucleotide is enclosed in a carrier such as cationic liposome effective for introducing a medicament into a cell (e.g., PCT WO99/20283, PCT WO99/48531).
It is known that when a polynucleotide is hydrolyzed to shorten the chain length as described above, some phosphate groups cause intramolecular rearrangement from 3′ position to 2′ position through a mechanism called pseudo rotation simultaneously with the chain-shortening (see, e.g., “Protein Nucleic acid Enzyme”, Vol. 40, No. 10, pp. 1323 to 1332 (1995)). As a result, a portion of 3′-5′ phosphodiester bonds in the chain-shortened polynucleotide molecule are replaced by 2′-5′ phosphodiester bonds. It has never been known whether or not such a phosphate rearrangement phenomenon would affect the pharmacological action.